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Risk of breast cancer with HRT depends on therapy type and duration

BMJ 2022; 376 doi: (Published 08 March 2022) Cite this as: BMJ 2022;376:o485

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Use of hormone replacement therapy and risk of breast cancer

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Rapid Response:

Risk of breast cancer with HRT: progesterone is safer than progestins

Dear Editor,

The lowest risk of breast cancer in women prescribed HRT/MHT is actually, when progesterone, as opposed to progestins (synthetic progestogens), is used.

A large French study which assessed and compared the association between different HRTs and breast cancer risk, followed up 80,377 women for an average of 8.1 post-menopausal years, and found that compared with HRT never-use, there was no increased risk of breast cancer for oestrogen-progesterone (relative risk 1.00), whereas those using oestrogen plus progestins had a 16-69% increased risk of breast cancer (depending on the progestin used). (1)

Another French study also found that breast cancer risk differed by type of progestogen among current users of oestrogen-progestogen therapies. No increased risk was apparent among users of oestrogen + micronized progesterone (in fact, there was a 20% lower risk for any duration of use, compared with never-users of MHT). (2)

A meta-analysis of studies of postmenopausal women using progesterone vs. synthetic progestins in combination with oestrogen found that progesterone-oestrogen was associated with a 33% lower risk of breast cancer compared with progestins. (3)

The meta-analysis of the worldwide epidemiological evidence published in the Lancet in 2019 found that oestrogen-micronised progesterone combination for <5 years of use had a relative risk of breast cancer of 0.91 compared with women who had never used HRT [although for some reason this data was buried in the supplementary appendix]. (4)

Thus, it seems clear that oestrogen-progesterone carries the lowest risk of breast cancer, and should be the HRT of choice.

1. Breast Cancer Res Treat, 2008;107(1):103-11
2. PLoS ONE, 2013; 8(11): e78016. doi:10.1371/journal.pone.0078016
3. Systematic Reviews, 2016; 5:121; DOI 10.1186/s13643-016-0294-5
4. The Lancet, 2019; Published online August 29:; appendix p 45

Competing interests: No competing interests

17 March 2022
Peter J Lewis
GP with special interest in integrative medicine
Vale Medical Practice, Brookvale, NSW 2100, Australia